This proposal for a Clinical Investigator Award will investigate the regulation of growth hormone (GH) secretion by examining the effects of the cholinergic neural system on the production and release of GH-releasing hormone (GHRH) and somatostatin (SS) from the hypothalamus. Effects of cholinergic agonists and antagonists on acute release of GHRH and SS will by assessed by perifusion of rat hypothalami. Effects of cholinergic agents on transcriptional regulation of GHRH and SS will be assessed by mRNA quantification using dot blot and in situ hybridization of radiolabelled oligodeoxyribonucleotide probes. The ability of GHRH- and SS-containing cells to respond directly to cholinergic stimuli will be assessed by double-labelling tissue for cholinergic receptors and for GHRH or SS mRNA content. Evidence of feedback regulation between GHRH and SS secretion will be sought. These studies will elucidate specific mechanisms of neurotransmitter control of GH release and general principles of neuroendocrine secretion. The principal investigator, Dr. Verena Jorgensen, has pursued an academic research career in pediatric endocrinology through a three year research fellowship at Duke University and two years at the University of South Florida. The proposed studies will expand her previous skills in binding and hormonal release studies to include RNA extraction, dot blot, Northern blot and in situ hybridization. Collaboration with members of the departments of biochemistry and molecular biology, anatomy, pharmacology, and pediatric endocrinology will provide support, experience and equipment for the execution of these experiments. In addition, an off-campus advisor will be available to share his many years of experience in neuroendocrine studies. The opportunity to acquire techniques in molecular biology and to concentrate on laboratory studies for five years will further the awardee's evolution into an independent researcher.